Genetic modelling of the PTEN/AKT pathway in cancer research.
The focus on targeted therapies has been fuelled by extensive research on molecular pathways and their role in tumorigenesis. Novel models of human cancer have been created to evaluate the role of specific genes in the different stages of cancer. Currently, mouse modelling of human cancer is possible through the expression of oncogenes, specific genetic mutations or the inactivation of tumour suppressor genes, and these models have begun to provide us with an understanding of the molecular pathways involved in tumour initiation and progression at the physiological level. Additionally, these mouse models serve as an excellent system to evaluate the efficacy of currently developed molecular targeted therapies and identify new potential targets for future therapies. The PTEN/AKT pathway is implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Deregulation of the PTEN/AKT pathway is a common event in human cancer. Despite the abundant literature, the physiological role of each element of the pathway has begun to be uncovered thanks to genetically engineered mice. This review will summarise some of the key animal models which have helped us to understand this signalling network and its contribution to tumorigenesis.
Renner
Oliver
O
Experimental Therapeutics Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Blanco-Aparicio
Carmen
C
Carnero
Amancio
A
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012107:Research Design; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C494929:PTEN protein, human